The invention relates generally to a method of treating a mammalian skin disorder associated with sebaceous follicles. More particularly, the invention relates to a method of treating acne in a mammal using a beam of laser or incoherent radiation.
There are a variety of disorders associated with sebaceous follicles (also referred to herein as sebaceous follicle disorders) known to afflict mammals, in particular, humans. The disorders usually are associated with aberrations (for example, structural or functional aberrations) of the sebaceous follicles. In humans, sebaceous follicles, although present over most of the body surface, usually are largest and most dense on the face, chest and upper back. Accordingly, sebaceous follicle disorders predominantly affect these areas of the human body.
Probably the most pervasive sebaceous follicle disorder in the United States is acne, which affects between 40 to 50 million individuals in the United States (White G M, (1998) xe2x80x9cRecent findings in the epidemiologic evidence, classification, and subtypes of acne vulgaris,xe2x80x9d J. AM. ACAD. DERMATOL. 39(2 Pt 3): S34-7). Acne occurs with greatest frequency in individuals between the ages of 15 and 18 years, but may begin at virtually any age and can persist into adulthood. In the 12 to 17-year old range, the incidence has been reported to be 25% (Strauss J S, (1982) xe2x80x9cSkin care and incidence of skin disease in adolescence,xe2x80x9d CURR. MED. RES. OPIN. 7(Suppl 2):33-45). Acne is a disorder characterized by inflammatory, follicular, papular and/or pustular eruptions involving the sebaceous follicles (Stedman""s Medical Dictionary, 26th edition, (1995) Williams and Wilkins). Although there are a variety of disorders that fall within the acne family, for example, acne conglobata, acne rosacea, and acne vulgaris, acne vulgaris probably is the most notable and commonly known form of acne. Acne vulgaris occurs with greatest frequency in individuals between the ages of 15 and 18 years, but may begin at virtually any age and can persist into adulthood. Because acne vulgaris can lead to permanent scarring, for example, facial scarring, this form of acne can have profound and long-lasting psychological effects on an afflicted individual. Furthermore, pustule formation and scarring can occur at an age when the potential impact on an individual is greatest. As a result, enormous amounts of money (i.e., on the order of billions of dollars) are spent annually in the United States on various topical and systemic acne treatments. These treatments often are employed without the guidance or supervision of a physician.
Acne vulgaris typically results from a blockage of the opening of the sebaceous follicle. It is believed that both (i) the amount of sebum, a lipid, keratin and cellular debris containing fluid, produced and secreted by the sebaceous glands and (ii) bacteria, namely, Propionibacterium acnes (P. acnes) which metabolize lipids in the sebum, play a role in formation and development of acne vulgaris. The basic lesion of acne vulgaris is referred to as a comedo, a distension of the sebaceous follicle caused by sebum and keratinous debris. Formation of a comedo usually begins with defective keratinization of the follicular duct, resulting in abnormally adherent epithelial cells and plugging of the duct. When sebum production continues unabated, the plugged follicular duct distends. A blackhead (or open comedo) occurs when a plug comprising a melanin containing blackened mass of epithelial debris pushes up to opening of the follicular duct at the skin surface. A whitehead (or closed comedo) occurs when the follicle opening becomes very tightly closed and the material behind the closure ruptures the follicle causing a low-grade dermal inflammatory reaction. Accordingly, some comedones, for example, in acne vulgaris, evolve into inflammatory papules, pustules, nodules, or chronic granulomatous lesions. Proliferation of P. acnes can result in the production of inflammatory compounds, eventually resulting in neutrophil chemotaxis (Skyes and Webster (1994) Drugs 48: 59-70).
At present, acne patients may receive years of chronic topical or systemic treatments. Current treatment options include, for example, the use of topical anti-inflammatory agents, antibiotics and peeling agents, oral antibiotics, topical and oral retinoids, and hormonal agonists and antagonists. Topical agents include, for example, retinoic acid, benzoyl peroxide, and salicylic acid (Harrison""s Principles of Internal Medicine, 14th edition, (1998) Fauci et al., eds. McGraw-Hill). Useful topical antibiotics include, for example, clindamycin, erythromycin, and tetracycline and useful systemic antibiotics include, for example, erythromycin, tetracycline, and sulphanilamides (see, for example, U.S. Pat. Nos. 5,910,493 and 5,674,539). Administration of the systemic retinoid, isotretinion, has demonstrated some success in the treatment of acne (Harrison""s Principles of Internal Medicine, 14th edition, (1998) Fauci et al., eds. McGraw-Hill). Studies indicate that this drug decreases sebaceous gland size, decreases the rate of sebum production and/or secretion, and causes ductal epithelial cells to be less adherent, thereby preventing precursor lesions of acne vulgaris (Skyes and Webster (1994) supra). Side-effects, however, include dry mouth and skin, itching, small red spots in the skin, and eye irritation. A significant concern about oral retinoids is their possible teratogenicity (Turkington and Dover (1996) SKIN DEEP: AN A-Z OF SKIN DISORDERS, TREATMENT AND HEALTH FACTS ON FILE, Inc., New York, page 9). In addition, a variety of hormone-related, for example, corticosteroid anti-inflammatory therapies have been developed for the treatment of acne. These therapies can be expensive and most are associated with deleterious systemic or localized side-effects (Strauss (1982) xe2x80x9cSkin care and incidence of skin disease in adolescence,xe2x80x9d CURR. MED. RES. OPIN. 7(Suppl 2): 33-45).
Because the foregoing therapies generally do not affect the structure and/or function of sebaceous follicles associated with the disease, the treatments remain non-curative. In other words, the disorder may recur after cessation of therapy. The result can be years of chronic therapy, and potential scarring for the patient, and enormous associated health care costs.
In recent years, a variety of laser-based methodologies for treating acne have been developed. The methods generally involve the combination of laser radiation and either an exogenous or endogenous chromophore present in the target tissue so that the laser light is absorbed preferentially in the target tissue causing morphological changes to the sebaceous follicle and/or causing a reduction of sebum production. For example, U.S. Pat. No. 5,817,089 describes a laser-based method for treating acne requiring topical application of a light absorbing chromophore, for example, micron graphite particles dispersed in mineral oil, onto skin needing such treatment. Similarly, U.S. Pat. No. 5,304,170 also describes a laser-based method for treating acne in which target cells contain greater amounts of a light absorbing chromophore, for example, the carotenoid xcex2-carotene, relative to lesser or non-pigmented surrounding cells. In the chromophore based methods it can be difficult to get sufficient chromophore in the target region to elicit selective tissue damage and the method may still damage the outer layers of the skin resulting in scarring.
The present invention addresses the foregoing problems and provides a method for treating sebaceous follicle disorders of mammalian skin, for example, human skin. The method permits treatment of the sebaceous follicle disorder while at the same time preserving surrounding skin tissue, for example, skin epidermis. The invention offers numerous advantages over existing treatment protocols. For example, the method provides a long lasting treatment which persists long after treatment has ceased. Furthermore, the method minimizes trauma and scar formation at the skin surface, reduces side-effects, such as, pain, erythema, edema, and blistering, which can result from other treatments, and can also minimize pigmentary disturbances of the skin.
In one aspect, the present invention features a method of treating a sebaceous follicle disorder in a preselected region of mammalian skin, the preselected region having at least one lesion characteristic of the disorder disposed therein. The method comprises the steps of (a) cooling an exposed surface of the preselected region of the mammalian skin and (b) applying heating energy to the preselected region in an amount sufficient to ameliorate the lesion disposed within the preselected region. Without wishing to be bound by theory, it is contemplated that amelioration of the lesion can result from the destruction of the sebaceous follicle, structural changes to the sebaceous follicle to reduce the possibility of pore blockage, and/or reduction of sebum production by the sebaceous gland associated with the sebaceous follicle. As will be discussed in more detail below, the cooling step can be performed prior to and/or contemporaneous with the step of applying the heating energy. Furthermore, it is contemplated that the cooling step can be performed after the heating step.
In a preferred embodiment, the heating energy is provided by means of a beam of radiation (for example, coherent or incoherent radiation), microwaves, ultrasound or radio frequency (RF) current. More preferably, the heat energy originates from a source of radiation, and most preferably from a source of coherent radiation. The source of the coherent radiation can be, for example, a pulsed, scanned, or gated continuous wave (CW) laser.
In a preferred embodiment, the beam of radiation comprises a wavelength in the range from about 0.6 microns to about 1.8 microns, more preferably in the range from about 1.2 to about 1.6 microns, and more preferably in the range from about 1.3 to about 1.6 microns. Most preferably, the beam has a nominal wavelength of about 1.5 microns. The beam preferably has either a fluence in the range from about 5 to about 500 joules per square centimeter, and more preferably in the range from about 10 to about 150 joules per square centimeter, or a power density in the range of about 1 to about 10,000 watts per square centimeter, and more preferably in the range from about 5 to about 5,000 watts per square centimeter.
During practice of the invention, application of the heating energy can induce thermal changes to the portion of the dermis where sebaceous follicles reside. This heating may result in the destruction of the sebaceous follicle or the sebaceous gland associated with the follicle, cause structural changes in the follicle to reduce the likelihood of blockage and/or reduce the level of sebum production. The cooling step serves to preserve the epidermis and the dermis overlaying the sebaceous gland containing region of the skin thereby reducing side-effects such as pain, erythema, edema, and blistering which otherwise may result from exposure to the beam of radiation. The cooling step can be performed prior to, contemporaneous with, or after application of the energy to the target region, or alternatively the cooling can result from a combination of such cooling steps.
Cooling can be achieved using many different techniques known and used in the art. For example, cooling can be achieved by blowing a stream of cold air or gas onto the target site, by applying a cold liquid onto the target site, by conductive cooling using a cold contact surface applied to the target site, or by evaporative cooling using a low boiling point liquid applied to the target tissue. In a preferred embodiment, cooling is achieved using evaporative cooling technologies by means of, for example, a commercially available dynamic cooling device (DCD).
Practice of the invention can be prophylactic or can be performed to ameliorate one or more symptoms or lesions associated with the various sebaceous follicle disorders. Exemplary sebaceous follicle disorders include, for example, acne vulgaris, acne rosacea, acne conglobata, seborrhea, sebaceous adenoma and sebaceous gland hyperplasia. The present invention, however, is particularly useful in the treatment of acne, more specifically, the treatment of acne vulgaris.
Sebaceous follicle disorders, for example, acne vulgaris and seborrhea, sometimes are associated with the overproduction of sebum. For example, in acne vulgaris, the level of sebum production by sebaceous glands has been correlated with the severity of the disorder (Leyden (1995) J. AM. ACAD. DERM. 32: S15-25). Accordingly, in a preferred embodiment, the method of the invention lowers or even eliminates sebum production by sebaceous glands of sebaceous follicles relative to untreated sebaceous follicles. In another embodiment, treatment can increase the size of the opening of the sebaceous follicle, in the proximity of the infundibulum, thereby affecting sebum flow and/or minimizing the likelihood of blockage of the sebaceous follicle. Furthermore, treatment may destroy or inactivate the sebaceous follicle thereby eliminating sebum production in that follicle.
Application of the heating energy can reduce the size of one or more lesions, for example, comedones in the case of acne vulgaris, disposed within the preselected region. Furthermore, application of the heating energy can also reduce the density of the lesions disposed within the preselected region. In cases in which skin inflammation can be associated with the lesion, for example, in severe cases of acne vulgaris and acne conglobata, the application of the heating energy may reduce the inflammation associated with the lesion. The benefit of treatment, for example, reduction in the number of or elimination of skin lesions, may become apparent days to weeks after the treatment. Furthermore, it is contemplated that in certain cases, e.g., severe cases, of sebaceous follicle disorders, multiple rounds of treatment, for example, two to ten separate rounds of treatment, may be required to treat an individual satisfactorily.
It is contemplated that, based upon choice of appropriate cooling and/or heat energy parameters, it is possible to create thermally induced changes of sebaceous follicles in the absence of an exogenous energy absorbing material. However, under some circumstances, for example, when heating is accomplished by the application of a radiation beam, optimal treatment may be facilitated by applying to the preselected region prior to exposure to the radiation beam a radiation absorbing material, for example, a chromophore photoexcited by the radiation. The radiation absorbing material may be administered systemically to the mammal or applied topically to the preselected region prior to exposure to the radiation beam.